The transdermal route of parenteral delivery of drugs provides many advantages over other administrative routes, and transdermal systems for delivering a wide variety of drugs or other beneficial agents are described in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,731,683; 3,797,494; 4,031,894; 4,201,21 1; 4,286,592; 4,314,557; 4,379,454; 4,435,180; 4,559,222; 4,573,995; 4,588,580; 4,645,502; 4,704,282; 4,788,062; 4,816,258; 4,849,226; 4,908,027; 4,943,435; and 5,004,610, for example. The disclosures of the above patents are incorporated herein by reference. In many instances, drugs that would appear to be ideal candidates for transdermal delivery are found to have such low permeability through intact skin that they cannot be delivered at therapeutically effective rates from reasonably sized systems.
In an effort to increase skin permeability, it has been proposed to pretreat the skin with various chemicals or to concurrently deliver the drug in the presence of a permeation enhancer. Various materials have been suggested for this purpose, as described in U.S. Pat. Nos. 3,472,931, 3,527,864, 3,896,238, 3,903,256, 3,952,099, 4,046,886, 4,130,643, 4,130,667, 4,299,826, 4,335,115,4,343,798, 4,379,454, 4,405,616 and 4,746,515, all of which are incorporated herein by reference; British Pat. No. 1,001,949; and Idson, Percutaneous Absorption, J. Pharm. Sci., Vol. 64, No. b6, June 1975, pp 901-924 (particularly 919-921).
Many permeation enhancers interact adversely with other components of transdermal devices. One problem is that many permeation enhancers are not compatible with medically acceptable contact adhesives. This can cause, among other problems, cohesive failure of adhesives. Additionally, the permeation enhancers can partition into other components in the system. This can cause devices to delaminate or it can cause instability of the device, thus shortening its shelf life.
Another problem related to adhesives of transdermal systems is the problem of adhesive failure resulting in water induced fall-off of the system. Adhesive failure may be caused by accumulation of the permeation enhancer at the skin-adhesive interface. As water accumulates on the skin, particularly during exercise or bathing, the interaction between the water and the permeation enhancer causes a soapy solution to form at the interface thereby causing the transdermal system to fall off.
This invention utilizes a novel combination of permeation enhancer(s) and a poly-N-vinyl amide. The novel combination produces a significant and surprising improvement in transdermal fluxes, drug utilization, storage stability, and improved adhesion over previous transdermal devices.